Expression of Granulysin and FOXP3 in Cutaneous T Cell Lymphoma and Sézary Syndrome

Background: Multiple complex pathways are operable in the evolution of cutaneous T cell lymphomas(CTCLs). These pathways involve interaction between neoplastic T cells and cells of the immune system (especiallydendritic cells and the non-malignant T cells). Granulysin is a proinflammatory antimicrobial peptide whichhas an immune alarmin function, activating dendritic cells, as well as an active role in tumor immunology andprognosis. FOXP3+ regulatory T cells Tregs are an important player in the immune system. Much controversy isfound in the literature about the role of Tregs in CTCL. Aim: The present study aimed to investigate the expressionof granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and itsleukemic form Sézary syndrome (SS). Materials and Methods: Immunohistochemical expression of granulysinand FOXP3 were assessed in lesional skin biopsies taken from 58 patients (4 large plaque parapsoriasis, 48 MFand 6 SS). Results: Granulysin positivity was cytoplasmic and higher in MF than in parapsoriasis en plaqueand higher in the more advanced stages of MF (p<0.001). All groups showed significant differences betweeneach other except between MF tumor stage and SS. FOXP3 positivity was nuclear and higher in early stageMF (plaque and patch stages) than in tumor stages and SS (p<0.001). However the FOXP3 count was lowerin parapsoriasis en plaque than in other stages of MF. All the groups showed significant differences betweeneach other except between parapsoriasis and SS and between patch and plaque stages of MF. Conclusions: Thepresent study supports a role for granulysin in MF progression and proposes a novel hypothesis about the effectof FOXP3 +veTregs in the suppression of the activity of the neoplastic cells in MF.